Notes

Stress partition and microstructure inside size-segregating granular runs.
α,β-Thujone is a natural terpenoid found in many medicinal herbs, such as Artemisia absinthium (wormwood), that exhibits antioxidant, anti-diabetic, and anti-tumorigenic effects. α,β-Thujone has numerous functions; it serves as a food ingredient, cosmetic additive, and medicinal remedy. Although the therapeutic properties of α,β-thujone were previously revealed, a comprehensive description of the mechanisms of its anti-cancer potential in choriocarcinoma is yet to be provided. To our knowledge, this study is the first to demonstrate that α,β-thujone attenuates JEG3 and JAR choriocarcinoma cells through a caspase-dependent intrinsic apoptotic pathway. Moreover, α,β-thujone was demonstrated to induce a global mitochondrial defect and ER stress in choriocarcinoma by causing mitochondrial depolarization, calcium overload, and metabolic alterations, thereby leading to energy deprivation, which eventually contributes to the increase in apoptosis of choriocarcinoma cells. Herein, we also revealed the synergistic anti-cancer activity of α,β-thujone via its sensitization effect on paclitaxel in choriocarcinoma cells. Altogether, our findings suggest that α,β-thujone is a novel, natural pharmacological compound that can be used to treat human placental choriocarcinoma.CRISPR-mediated transcriptional activation, also known as CRISPR-on, has proven efficient for activation of individual or multiple endogenous gene expression in cultured cells from several species. However, the potential of CRISPR-on technology in preimplantation mammalian embryos remains to be explored. Here, we report for the first time the successful modulation of endogenous gene expression in bovine embryos by using the CRISPR-on system. As a proof of principle, we targeted the promoter region of either SMARCA4 or TFAP2C genes, transcription factors implicated in trophoblast lineage commitment during embryo development. We demonstrate that CRISPR-on provides temporal control of endogenous gene expression in bovine embryos, by simple cytoplasmic injection of CRISPR RNA components into one cell embryos. dCas9VP160 activator was efficiently delivered and accurately translated into protein, being detected in the nucleus of all microinjected blastomeres. Our approach resulted in the activation of SMARCA expression shortly after microinjection, with a consequent effect on downstream differentiation promoting factors, such as TFAP2C and CDX2. Although targeting of TFAP2C did not result in a significant increase in gene expression, in downstream CDX2 expression an induction was detected at day 2 after microinjection. Finally, we demonstrate that CRISPR-on system is suitable for gene expression modulation during the preimplantation period, since no detrimental effect was observed on microinjected embryo development. This study constitutes a first step towards the application of the CRISPR-on system for the study of early embryo cell fate decisions in cattle and other mammal embryos, as well as to design novel strategies that may lead to an improved trophectoderm development.BACKGROUND The novel coronavirus disease 2019 (COVID-19) pandemic is an urgent public health crisis, with epidemiologic models predicting severe consequences, including high death rates, if the virus is permitted to run its course without any intervention or response. Contact tracing using smartphone technology is a powerful tool that may be employed to limit disease transmission during an epidemic or pandemic; yet, contact tracing apps present significant privacy concerns regarding the collection of personal data such as location. OBJECTIVE The aim of this study is to develop an effective contact tracing smartphone app that respects user privacy by not collecting location information or other personal data. METHODS We propose the use of an anonymized graph of interpersonal interactions to conduct a novel form of contact tracing and have developed a proof-of-concept smartphone app that implements this approach. Additionally, we developed a computer simulation model that demonstrates the impact of our proposal on epidemic or pandemic outbreak trajectories across multiple rates of adoption. RESULTS Our proof-of-concept smartphone app allows users to create "checkpoints" for contact tracing, check their risk level based on their past interactions, and anonymously self-report a positive status to their peer network. Our simulation results suggest that higher adoption rates of such an app may result in a better controlled epidemic or pandemic outbreak. CONCLUSIONS Our proposed smartphone-based contact tracing method presents a novel solution that preserves privacy while demonstrating the potential to suppress an epidemic or pandemic outbreak. This app could potentially be applied to the current COVID-19 pandemic as well as other epidemics or pandemics in the future to achieve a middle ground between drastic isolation measures and unmitigated disease spread. ©Tyler M Yasaka, Brandon M Lehrich, Ronald Sahyouni. Originally published in JMIR mHealth and uHealth (http//mhealth.jmir.org), 07.04.2020.The world is experiencing the expansive spread of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in a global pandemic that is placing strain on health care, economic, and social systems. Commitment to implementing proven public health strategies will require bold public health leadership and courageous acts by politicians. Napabucasin cost Developing new innovative communication, mitigation, and health care approaches, particularly in the era of social media, is also clearly warranted. We believe that the best public health evidence must inform activities in three priority areas to stop this pandemic (1) coordinated and consistent stay-at-home orders across multiple jurisdictions, including potential nationwide mandates; (2) rapid scale-up of SARS-CoV-2 testing; and (3) improved health care capacity to respond. This editorial outlines those areas, the rationale behind them, and the call for innovation and engagement of bold public health leadership to empower courageous political action to reduce the number of deaths during this pandemic. ©Jodie L Guest, Carlos del Rio, Travis Sanchez. Originally published in JMIR Public Health and Surveillance (http//publichealth.jmir.org), 06.04.2020.N-methyl-d-aspartate receptor (NMDAR) antagonists, including ketamine and nitrous oxide, are currently intensely studied as rapid-acting antidepressant agents. Interestingly, both of these compounds are also drugs of abuse. Intravenous ketamine, a dissociative anesthetic that induces complex downstream effects via NMDARs, rapidly reduces depressive and suicidal symptoms in treatment-resistant depression (TRD), as demonstrated by several trials. Recently, the United States Food and Drug Administration (FDA) approved an intranasal version of ketamine (esketamine) for TRD. The United States Drug Enforcement Agency (DEA) lists ketamine as a Class III scheduled drug (moderate-low potential for physical and psychological abuse). The FDA has established a Risk Evaluation and Management Strategy (REMS) program to ensure proper drug storage, handling, dispensing, and monitoring intranasal esketamine to minimize misuse/abuse opportunities. Nitrous Oxide is a colorless, odorless, gas that has been in medical use for over 150 years. The mechanisms of action of nitrous oxide are not fully understood; however, it is known to act as a non-competitive inhibitor of NMDA-type glutamate receptors. Currently, nitrous oxide is used for inhalational general anesthesia and analgesia for short procedures. Inhaled nitrous oxide is also used recreationally, primarily by teens and young adults, but is not believed to have strong addiction potential. In contrast to ketamine, nitrous oxide is not a controlled substance and can be legally purchased without a prescription. A recent double-blind, prospective, cross-over study demonstrated that nitrous oxide reduced depressive symptoms in a group of severely ill TRD patients. Though this is a promising initial study, further investigation is needed. BACKGROUND There is a lack of information on the natural history of asymptomatic carotid artery stenosis (AsymCS) associated with cardiovascular diseases that require surgery. The aim of this study was to investigate risk factors for postoperative ipsilateral ischemic stroke and all-cause mortality after cardiovascular surgery in patients with AsymCS. METHODS Among 2158 patients who underwent cardiovascular surgery, 150 patients with AsymCS who didn't undergo carotid revascularization were included. The relationships between preoperative factors, including carotid intraplaque hemorrhage (IPH), and postoperative ipsilateral ischemic stroke and all-cause mortality were analyzed retrospectively. RESULTS During the median follow-up of 1087 days of 150 patients with 19 IPH, 12 (8.0%) and 21 (14.0%) encountered ipsilateral infarction and all-cause mortality, respectively. Multivariable Cox regression analyses indicated that IPH was significantly predictive of both ipsilateral infarction (hazard ratio [HR] 21.31, 95% confidence interval [CI], 4.98-91.17; P ≤.001) and all-cause mortality (HR 4.64, 95% CI, 1.61-13.34; P = .004). Another significant factor was peak systolic velocity for ipsilateral infarction with the cutoff velocity of 227 cm/s by the receiver-operating characteristic curve. CONCLUSIONS In this cohort of patients with AsymCS undergoing cardiovascular surgery, IPH had a close connection with a high risk of both postoperative ischemic stroke and mortality after cardiovascular surgery. V.Lysine acetylation is one of the most important post-translational modifications and is involved in multiple cellular processes in plants. There is evidence that acetylation may play an important role in light-induced de-etiolation, a key developmental switch from skotomorphogenesis to photomorphogenesis. During this transition, establishment of photosynthesis is of great significance. However, studies on acetylome dynamics during de-etiolation are limited. Here, we performed the first global lysine acetylome analysis for Zea mays seedlings undergoing de-etiolation, using nano liquid chromatography coupled to tandem mass spectrometry, and identified 814 lysine-acetylated sites on 462 proteins. Bioinformatics analysis of this acetylome showed that most of the lysine-acetylated proteins are predicted to be located in the cytoplasm, nucleus, chloroplast, and mitochondria. In addition, we detected ten lysine acetylation motifs and found that the accumulation of 482 lysine-acetylated peptides corresponding to 289 proteins changed significantly during de-etiolation. These proteins include transcription factors, histones, and proteins involved in chlorophyll synthesis, photosynthesis light reaction, carbon assimilation, glycolysis, the TCA cycle, amino acid metabolism, lipid metabolism, and nucleotide metabolism. Our study provides an in-depth dataset that extends our knowledge of in vivo acetylome dynamics during de-etiolation in monocots. This dataset promotes our understanding of the functional consequences of lysine acetylation in diverse cellular metabolic regulatory processes, and will be a useful toolkit for further investigations of the lysine acetylome and de-etiolation in plants.
Here's my website: https://www.selleckchem.com/products/napabucasin.html